1-182657603-C-A

Variant names:

• chr1-182657603-C-A
• rs4652741
• NM_001102450.3:c.193+8366G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102450.3(RGS8):​c.193+8366G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,642 control chromosomes in the GnomAD database, including 36,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36340 hom., cov: 29)
• Consequence: RGS8 NM_001102450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974
• Publications: 1 publications found

Genes affected

RGS8 (HGNC:16810): (regulator of G protein signaling 8) This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102450.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS8	NM_001102450.3	MANE Select	c.193+8366G>T		intron	N/A	NP_001095920.1	P57771-1
	RGS8	NM_033345.4		c.247+8366G>T		intron	N/A	NP_203131.1	P57771-2
	RGS8	NM_001369564.2		c.193+8366G>T		intron	N/A	NP_001356493.1	P57771-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS8	ENST00000515211.2	TSL:4 MANE Select	c.193+8366G>T		intron	N/A	ENSP00000511884.1	P57771-1
	RGS8	ENST00000258302.8	TSL:1	c.247+8366G>T		intron	N/A	ENSP00000258302.4	P57771-2
	RGS8	ENST00000367557.8	TSL:1	c.193+8366G>T		intron	N/A	ENSP00000356528.4	P57771-1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104198 AN: 151522 Hom.: 36336 Cov.: 29

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.687 AC: 104233 AN: 151642 Hom.: 36340 Cov.: 29 AF XY: 0.687 AC XY: 50879 AN XY: 74092

African (AFR) AF: 0.581 AC: 23964 AN: 41280

American (AMR) AF: 0.655 AC: 9977 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3466

East Asian (EAS) AF: 0.610 AC: 3141 AN: 5152

South Asian (SAS) AF: 0.730 AC: 3493 AN: 4788

European-Finnish (FIN) AF: 0.777 AC: 8187 AN: 10530

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51011 AN: 67880

Other (OTH) AF: 0.670 AC: 1408 AN: 2102

Alfa AF: 0.724 Hom.: 125078

Bravo AF: 0.668

Asia WGS AF: 0.700 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4652741; hg19: chr1-182626738;